GeroScience最新文献

{"title":"Optimizing Statin Therapy in Older Adults: A Systematic Review of Dosing, Titration, and Combination Strategies.","authors":"Anna Artner,Romána Zelkó,Balázs Hankó","doi":"10.1007/s11357-025-01772-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01772-w","url":null,"abstract":"Statins are crucial in lipid-lowering therapy for reducing atherosclerotic cardiovascular disease (ASCVD) risk. However, rhabdomyolysis, a rare but severe side effect, disproportionately affects frail, older adults with polypharmacy and multiple comorbidities. Current guidelines for adjusting statin dosages in older adults lack clarity. To evaluate statin use in the geriatric population, assess benefit-risk ratios, and analyze dosage regimens through a systematic literature review. A comprehensive search was conducted in PubMed, Scopus, Web of Science, and EBSCO databases. Eleven original studies involving 566,509 patients were included. The review was registered on PROSPERO (CRD42024587259). Statin therapy was associated with a lower risk of cardiovascular disease compared to placebo. When adjusted during treatment, higher-intensity statins appeared to provide greater benefits than fixed low-dose statins, while the likelihood of side effects remained similar. Using ezetimibe and statins further improved outcomes and was linked to fewer side effects. Adherence-improving techniques were crucial, especially in older adults. Individualized statin dosing, considering titration, combination therapy, and adherence strategies, is essential for maximizing benefits and minimizing risks in older adults. While statins effectively reduce CVD risk, careful consideration of patient-specific factors is necessary when prescribing to older adults.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide riboside treatment enhances stress sensitivity and modulates hematological dynamics in aged mice.","authors":"Luka Culig,Amogh Kashyap,Wakako Kuribayashi,Quia C Claybourne,Isabel Beerman","doi":"10.1007/s11357-025-01793-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01793-5","url":null,"abstract":"Nicotinamide riboside (NR) is a precursor to NAD+, a vital molecule for cellular energy metabolism whose levels decline with age. Aging is associated with loss of cognitive and immune function, alterations in hematological parameters, and increased vulnerability to stress. Although NR supplementation can mitigate age-related declines, it remains uncertain whether these positive effects persist when the organism is exposed to chronic physiological stress. We investigated this by exposing aged mice to NR supplementation alongside daily physiological stress and assessed various indices before and after treatment. Our results revealed that 6 weeks of NR supplementation protected against stress-induced thrombocytopenia and increased the frequencies of B and T cells. However, NR also heightened stress sensitivity, as evidenced by increased anxiety-like behaviors, while not affecting cognitive function. These findings suggest a dual role for NR in potentially enhancing immune function while exacerbating behavioral responses to stress. Future research on NR should consider stress as a variable to optimize its therapeutic usage in aging populations.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"30 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum ACE2 activity as a novel biomarker of assessment of severe aortic stenosis.","authors":"Anita Kurczina,Arnold Péter Ráduly,Ivetta Mányiné Siket,Zsófia Pólik,Bertalan Kracskó,Attila Béla Kertész,Ágnes Balogh,Andrea Molnár,Tibor Fülöp,Laura Antal,Csaba Ötvös,Miklós Fagyas,Tamás Szerafin,Attila Tóth,Zoltán Papp,Zoltán Csanádi,Attila Borbély","doi":"10.1007/s11357-025-01792-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01792-6","url":null,"abstract":"Aortic stenosis (AS) is the most prevalent valve disease in developed countries, with its incidence rising in the aging population. The current criteria for aortic valve replacement (AVR) are based on subjective symptoms and left ventricular ejection fraction (LVEF), which may not adequately reflect left ventricular (LV) dysfunction. This highlights the necessity for objective biomarkers to evaluate subclinical LV dysfunction. Serum angiotensin-converting enzyme 2 (sACE2) has emerged as a promising novel biomarker for cardiovascular diseases. To investigate the association between sACE2 activity and different flow-grade categories of severe AS, compare it with the traditional biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP), and assess the utility of sACE2 as a biomarker for AS. sACE2 and NT-proBNP were measured in 175 patients (97 male, 78 female, mean age 75 ± 8 years) diagnosed with severe AS (aortic valve area, AVA ≤ 1 cm2). Patients were classified into 5 groups depending on LV flow state and pressure gradient levels: normal flow-low gradient (NF-LG), normal flow-high gradient (NF-HG), low flow-high gradient (LF-HG), low flow-low gradient (LF-LG), and paradoxical low flow-low gradient (PLF-LG) AS. Both biomarkers showed a general increase with advanced stages of severe AS (NF-LG: 65.0 ± 3.5 U/ml; LF-LG: 148.1 ± 16.8 U/ml; P < 0.05 for sACE2 and NF-LG: 687 ± 193 pg/ml; LF-LG: 5966 ± 1076 pg/ml; P < 0.05 for NT-proBNP). Notably, PLF-LG patients exhibited NT-proBNP levels similar to NF groups (PLF-LG: 1010 ± 218 pg/ml). Both biomarkers negatively correlated with LVEF and AVA. Receiver operating characteristic (ROC) analysis revealed that sACE2 provides incremental value over NT-proBNP in detecting subclinical LV dysfunction, with a 44% specificity for sACE2 compared to 6% for NT-proBNP at 98,67% sensitivity. The assessment of sACE2 activity in patients with AS provides valuable insights into disease stage and progression, supporting clinical decision-making and optimizing the timing of AVR. Furthermore, sACE2 activity serves as a moderately sensitive blood biomarker for identifying patients at risk of AS.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of progerin enhances disease-related endpoints in a tau seeding reporter cell system.","authors":"Zhuang Zhuang Han,Sang-Gyun Kang,Erik Gomez-Cardona,Serene Wohlgemuth,Klinton Shmeit,Luis Arce,Jiri G Safar,Olivier Julien,David Westaway","doi":"10.1007/s11357-025-01737-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01737-z","url":null,"abstract":"Sporadic Alzheimer's disease and some forms of frontotemporal lobar degeneration (FTLD-tau) are neurological disorders of later life where cognitive deficits follow from the progressive accumulation of microtubule-associated tau protein. Disease-related tau accumulation is marked by altered subcellular distribution and rearrangement of this natively unstructured protein into alternative conformational forms, including highly organized fibrillar assemblies. With a partial analogy to effects seen in prion diseases, pathological tau conformers have a templating activity called seeding that may be measured in cellular and cell-free systems. Moreover, cellular systems and disease models can recapitulate \"strain effects\" wherein the same tau amino acid sequence can adopt markedly different conformations. Here we analyzed FTLD-tau conformers in cellular reporter systems expressing a pro-aging mutant form of the lamin A protein termed \"progerin.\" Measured versus the baseline performance of a reporter system based on HEK293 cells, the addition of tau burden or progerin expression produced only mild changes in proteomic analyses or morphology, whereas application of both stressors produced a notable shift in ER stress and homeostasis, including increased levels of DNAJC10 and DNAJA2. The phenotypic effects scored here appear unrelated to the generation of new tau strains or to the type of strain input, insofar as progerin-expressing cells were more responsive to tau seeding by diverse brain samples containing different populations of tau conformers. Thus, premature aging and disease-associated tau conformers can exhibit an additive relationship in a model system.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"84 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing retrogenesis and physiological explanations for tract-wise white matter aging: links to developmental order, fiber calibre, and vascularization.","authors":"Tyler D Robinson, Jordan A Chad, Yutong L Sun, Paul T H Chang, J Jean Chen","doi":"10.1007/s11357-025-01773-9","DOIUrl":"10.1007/s11357-025-01773-9","url":null,"abstract":"<p><p>To understand observed spatial distributions of white-matter (WM) aging, developmentally driven theories termed \"retrogenesis\" have gained traction, positing that WM tract development order predicts order of declines, with later developing regions expected to deteriorate first, i.e., \"last-in-first-out.\" Alternatively, regions that develop most rapidly may decline most rapidly in aging, i.e., \"gains-predict-loss.\" The validity of such theories remains uncertain, partly due to lack of clarity in defining developmental order. Recent findings suggest that WM aging is also associated with physiological parameters such as perfusion and fiber size. Here, we address the extent to which degrees of WM aging are determined by development trajectory (i.e., retrogenesis) and/or physiological states. We obtained microstructural and perfusion data from the Human Connectome Project in Aging (HCP-A), complemented by a meta-analysis involving maps of fiber calibre and macrovascular volume. Our results suggest (1) myelination development order explains more associations with WM health than prenatal emergence order; (2) earlier-myelinating tracts exhibit higher microstructural integrity and less susceptibility to microstructural deterioration in aging but lower perfusion and longer arterial-transit times (ATT), suggestive of collateral blood supply; (3) earlier-emerging tracts show longest ATT and greatest ATT increase across aging; (4) tracts with larger axons and higher macrovascular density in young adulthood show longer ATT and less susceptibility to microstructure/perfusion degeneration irrespective of developmental order; and (5) negligible support for \"gains-predict-loss.\" These findings were sex-dependent in a tract-specific manner. Future work will investigate the role of macrovascular collateral flow and tract-wise influences of metabolic demand.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outdoor light at night and neuropsychiatric symptoms in dementia.","authors":"Manuela Tondelli,Tommaso Filippini,Giulia Vinceti,Najara Iacovino,Teresa Urbano,Sofia Costanzini,Francesca Despini,Claudia De Luca,Simona Tondelli,Marco Vinceti,Annalisa Chiari,Giovanna Zamboni","doi":"10.1007/s11357-025-01745-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01745-z","url":null,"abstract":"There is growing interest about the relation between exposure to artificial light at night (LAN) and mental health. This study aims, for the first time, to explore the association between LAN exposure and neuropsychiatric symptoms in individuals with dementia, investigating its role as a potential environmental risk factor. We collected data about 150 patients with dementia in Modena, Italy. We assessed LAN exposure using satellite imagery, while neuropsychiatric symptoms were evaluated through the Neuropsychiatric Inventory (NPI), a caregiver-administered questionnaire measuring the presence and severity of psychiatric symptoms. We used logistic regression models to examine associations between LAN exposure and neuropsychiatric features. Higher LAN exposure was associated with increased risk of psychiatric symptoms, particularly in the domains of psychosis and sleep disturbances. Specifically, individuals exposed to LAN levels above the median (LAN median = 26.32 nW/cm2/sr) demonstrated an elevated risk of delusions, hallucinations, and sleep disturbances (OR = 2.09, 95% CI 0.03-4.25), compared to those in the \"below the median\" category. Associations with other symptom domains, such as apathy and affective disturbances, showed weaker associations. Our findings indicate that artificial nighttime light exposure may negatively impact the mental well-being of individuals with dementia, potentially exacerbating psychotic symptoms and sleep disturbances. However, caution is warranted when interpreting these results due to the limited sample size and the possibility of unexamined residual confounding.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"12 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of life in end of life.","authors":"Lavinia Valeriani, Barbara Carrano, Fabrizio Vecchio","doi":"10.1007/s11357-025-01781-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01781-9","url":null,"abstract":"<p><p>Assessing quality of life (QOL) in end-of-life patients is vital for understanding the complex impacts of terminal illnesses on individual well-being. This study aims to compare two widely used QOL assessment tools: the Karnofsky Performance Status Scale (KPSS) and the Short-Form-36 (SF-36) Health Survey among patients with late-stage diseases. KPSS, a clinician-rated scale measuring functional capacity, provides an objective perspective on a patient's clinical status. Conversely, the SF-36 offers a patient-reported overview across eight dimensions, including physical and mental health. The study enrolled 68 patients with an average Karnofsky score of about 37. Results demonstrate a significant interaction between Karnofsky scores and SF-36 dimensions, indicating that patients with higher Karnofsky scores reported better physical, social, and emotional functioning. Strong positive correlations were found between high Karnofsky scores and specific SF-36 components, including Physical Functioning, Role Physical, and Social Functioning, suggesting that these aspects critically influence overall QOL. Notably, no correlation was identified between age and KPSS, highlighting that disease severity rather than age impacts QOL. Findings underscore the complementary roles of KPSS and SF-36 in assessing QOL in terminally ill patients; while some measures in SF-36 aligned closely with KPSS, others offered essential insights into patient experiences. This comprehensive approach emphasizes the need for robust QOL evaluations in palliative care, facilitating more patient-centered care aligned with individuals' values and needs.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of accelerometer-measured physical activity and sedentary behavior with unplanned hospitalization in older adults: a 6-year longitudinal study.","authors":"Joan Ars,Giorgi Beridze,Pau Farrés-Godayol,Laura M Pérez,Marco Inzitari,Amaia Calderón-Larrañaga,Anna-Karin Welmer","doi":"10.1007/s11357-025-01756-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01756-w","url":null,"abstract":"Regular physical activity (PA) and reduced sedentary behavior (SB) are well-established factors in promoting health and lowering the risk of chronic diseases. However, their relationship with unplanned hospitalizations remains unclear. Our aim was to investigate the associations between PA and SB parameters and the risk of unplanned hospital admissions, and the length of hospital stays in older adults. We analyzed data from 657 older adults aged ≥ 66 years from the Swedish SNAC-K study (2016-2018). The ActivPAL3 accelerometer was used to assess PA and SB. Multi-adjusted Cox and Laplace regressions were applied to examine PA and SB in relation to 6-year unplanned hospitalizations. Negative Binomial Regression models were employed to examine their associations with the length of hospital stays. For each 1000 steps/day, 100 low-intensity PA (LPA) walking events, and 15 min/day of time spent in moderate-to-vigorous PA (MVPA), the risk of unplanned admissions decreased (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.91-0.99, HR 0.77, 95%CI 0.61-0.96, and HR 0.91, 95%CI 0.83-1.00, respectively). Higher step counts and MVPA were also associated with shorter hospital stays (IRR per 1,000 steps: 0.91, 95% CI: 0.86-0.96; IRR per 15 min MVPA: 0.85, 95% CI: 0.75-0.96). No significant associations were found for SB or walking events with hospital stay in fully adjusted models. Our results suggest that higher step counts and greater participation in MVPA are associated with a reduced risk of hospital admissions and shorter hospital stays in older adults. Additionally, a greater number of LPA walking events was linked to lower risk of hospital admissions. These results support the promotion of regular walking and frequent PA as strategies to reduce healthcare burden in aging populations.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"280 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic information loss is a common feature of multiple diseases and aging.","authors":"Naor Sagy, Chieh Chang, Maayan Gal, Daniel Z Bar","doi":"10.1007/s11357-025-01767-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01767-7","url":null,"abstract":"<p><p>Aging is a major risk factor for a plethora of diseases. The information theory of aging posits that epigenetic information loss is a principal driver of the aging process. Despite this, the connection between epigenetic information loss and disease has not been thoroughly investigated. Here, we analyzed tissue-unique methylation patterns in healthy and diseased human organs, revealing that for several diseases these patterns degrade, regressing to a mean form. We interpret this as epigenetic information loss, where tissue-unique patterns erode. Information loss is not limited to diseases. Age-related erosion of unique methylation patterns was observed in some tissues and cells, while other tissues and cells diverged away from the mean. Our findings demonstrate that analyzing methylation patterns in tissue-unique sites can effectively distinguish between patients and healthy controls at least in some diseases, and underscore the role of epigenetic information loss as a common feature in various pathological conditions.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nervonic acid and 15-epi-PGA1 mediate systemic mitochondrial dysfunction in AD dementia.","authors":"Stephanie Robyn Heimler,K Allison Amick,Jaclyn Bergstrom,Marcos Moliné,Gargi Mahapatra,Suzanne Craft,Anthony J A Molina","doi":"10.1007/s11357-025-01776-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01776-6","url":null,"abstract":"Systemic mitochondrial dysfunction is apparent in the pathophysiology of Alzheimer's disease (AD). However, the factors driving bioenergetic decline remain unclear. This study utilized serum samples from older adults with normal cognition, mild cognitive impairment, and dementia to identify circulating molecules that can drive mitochondrial dysfunction in the context of AD. We used mass spectrometry to measure the abundance of lipid metabolites and applied tiered selection criteria to identify candidate \"mito-inhibitory\" molecules. These criteria were based on correlations with (1) in vitro bioenergetic effects of whole serum samples on naïve cells, (2) the bioenergetic capacity of blood cells from the serum donor, and (3) cognition, as measured by the modified mini-mental state exam. Mito-inhibitory lipid candidates were validated by examining their bioenergetic effects on neurons, myoblasts, and fibroblasts in vitro. Our results indicate that nervonic acid and 15-epi Prostaglandin A1 (15-epi-PGA1) are elevated in participants with dementia compared to those with normal cognition. Importantly, both metabolites inhibited mitochondrial function across multiple cell types in vitro. High resolution respirometric analyses reveal that inhibitory effects from lipid treatment occur via broad inhibition of the electron transfer system (ETS) with no change in overall mitochondrial content. This study provides insights into the mechanisms underlying systemic bioenergetic decline associated with AD dementia. The identification of circulating factors that drive mitochondrial bioenergetic decline may inform the development of mitochondrial therapeutics for AD.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}